title: Silver nanoparticles induce endoplasmatic reticulum stress response in zebrafish.
abstract: Silver nanoparticles (AgNPs) find increasing applications, and therefore humans and the environment are increasingly exposed to them. However, potential toxicological implications are not sufficiently known. Here we investigate effects of AgNPs (average size 120 nm) on zebrafish in vitro and in vivo, and compare them to human hepatoma cells (Huh7). AgNPs are incorporated in zebrafish liver cells (ZFL) and Huh7, and in zebrafish embryos. In ZFL cells AgNPs lead to induction of reactive oxygen species (ROS), endoplasmatic reticulum (ER) stress response, and TNF-α. Transcriptional alterations also occur in pro-apoptotic genes p53 and Bax. The transcriptional profile differed in ZFL and Huh7 cells. In ZFL cells, the ER stress marker BiP is induced, concomitant with the ER stress marker ATF-6 and spliced XBP-1 after 6h and 24h exposure to 0.5 g/L and 0.05 g/L AgNPs, respectively. This indicates the induction of different pathways of the ER stress response. Moreover, AgNPs induce TNF-α. In zebrafish embryos exposed to 0.01, 0.1, 1 and 5mg/L AgNPs hatching was affected and morphological defects occurred at high concentrations. ER stress related gene transcripts BiP and Synv are significantly up-regulated after 24h at 0.1 and 5mg/L AgNPs. Furthermore, transcriptional alterations occurred in the pro-apoptotic genes Noxa and p21. The ER stress response was strong in ZFL cells and occurred in zebrafish embryos as well. Our data demonstrate for the first time that AgNPs lead to induction of ER stress in zebrafish. The induction of ER stress can have several consequences including the activation of apoptotic and inflammatory pathways.
authors.affiliation: University of Applied Sciences and Arts Northwestern Switzerland, School of Life Sciences, Gründenstrasse 40, CH-4132 Muttenz, Switzerland.
authors.forename: Verena
authors.initials: V
authors.lastname: Christen
authors.forename: Martinus
authors.initials: M
authors.lastname: Capelle
authors.forename: Karl
authors.initials: K
authors.lastname: Fent
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004625:Embryo, Nonmammalian / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects* / Q000235:genetics; D004785:Environmental Pollutants / Q000737:chemistry / Q000493:pharmacokinetics / Q000633:toxicity*; D006801:Humans; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D053768:Metal Nanoparticles / Q000737:chemistry / Q000633:toxicity*; D010316:Particle Size; D017382:Reactive Oxygen Species / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D012834:Silver / Q000737:chemistry / Q000493:pharmacokinetics / Q000633:toxicity*; D013045:Species Specificity; D013054:Spectrophotometry, Atomic; D013499:Surface Properties; D014158:Transcription, Genetic / Q000187:drug effects; D015027:Zebrafish / Q000196:embryology
chemical_list: D004785:Environmental Pollutants; D017382:Reactive Oxygen Species; D012834:Silver
keywords: ER stress response; Nanoparticles; Silver nanoparticles; Toxicity; Zebrafish